In 1992, Lincoln defeated Alexander in the Democratic primary, by a margin of 61 to 39 percent. She subsequently won the general election, beating Republican Terry Hayes with 70% of the vote. Her election to the House coincided with the election of fellow Arkansan Bill Clinton as President of the United States.

She called herself a centrist Democrat[citation needed] and was among the minority of Democrats to support CAFTA. While in the House, she was one of only 17 Democrats to vote for the Teamwork for Employees and Managers Act of 1995 which sought to change federal employment laws. The law was vetoed by President Bill Clinton. She has voted in favor restricting class action lawsuits and tightening rules on personal bankruptcy. Lincoln was also one of the few Democrats in Congress to vote in favor of Bush administration's tax cuts and she supports the permanent elimination of the estate tax.

She was reelected to a second term under her married name, Blanche Lincoln, and served in the House of Representatives until 1997. Lincoln chose not to run for reelection in 1996; she was pregnant at that time.

Lincoln concentrated primarily on issues involving farmers and rural issues. She was one of the primary advocates of the Delta Regional Authority, which is designed to spur development in the lower Mississippi Delta region.

Lincoln became Arkansas's Senior Senator in January 2003, serving with Democrat Mark Pryor, who defeated incumbent Senator Tim Hutchinson in November 2002.

In 2004, Lincoln was re-elected, defeating Republican state Senator Jim Holt (R-Springdale) by 56%-to-44%, even as President Bush carried the state with 54% of the vote. She [9]received more than half a million votes, the highest total cast for any senatorial candidate in state history.

In 2007, Lincoln played a key role in brokering the compromise that led to passage of the Food, Conservation, and Energy Act of 2008. Also known as the “farm bill,” this legislation provides resources for nutrition, conservation, rural development, and renewable energy. Lincoln led the charge against defeating an amendment to the pending Farm Bill which would have capped government Agricultural subsidy payments at $250,000 per year, per farm. According to Lincoln, it was unfair to some farmers in her state, notably cotton growers. Even though the amendment passed (56–43), Lincoln threatened a filibuster if any amendment did not get a 60-vote majority, so the amendment was withdrawn after passage.

Lincoln's votes on health care appeared to be positioning her as a high-profile, "conservative Democrat", to avoid being perceived as a "liberal" by an Arkansas voting public that had turned increasingly Republican. In 2009 she spoke out in opposition to the pro-labor union bill known as the Employee Free Choice Act; this garnering her the praise of conservative interest groups like Americans for Tax Reform, but also bitter criticisms from labor unions, who publicly threatened to discourage Arkansas' remaining Democratic-leaning voters from voting for her.[12]

On December 9, 2010, Lincoln missed, by three minutes, a critical vote to repeal Don't ask, don't tell after a dental appointment and missed voting. A supporter of the bill, Sen. Joe Lieberman (I-CT), told reporters: "She was very frustrated and apologized to both of us." She said she would have voted for repeal had she made the vote.[14]

With the Obama Administration having become hugely unpopular in her home state, Lincoln's re-election strategy in 2010 was to depict herself to Arkansas voters as 'independent' of the Democrats. After first narrowly surviving a primary challenge by the state's then-Lieutenant Governor Bill Halter, Lincoln lost in November 2010 to Republican Congressman John Boozman by a landslide, 58%-to-37%.[15]

In 2004, Lincoln co-founded the Senate Hunger Caucus. The caucus was established to provide a bi-partisan forum for Senators and staff to discuss, advance and engage the Senate's work on national and international hunger and food insecurity issues.[16]

Lincoln also helped form the Moderate Dems Working Group, a coalition of moderate Senate Democrats whose stated goal is to work with Senate leadership and the administration toward finding bipartisan solutions to controversial political issues. In addition, she co-founded and currently co-chairs Third Way, a moderate think-tank whose self-described goals are "an economic agenda that is focused on growth and middle class success; a culture of shared values; a national security approach that is both tough and smart; and a clean energy revolution." [17]

Lincoln served on the Senate Finance Committee; Special Committee on Aging; Senate Committee on Energy and Natural Resources; Senate Social Security Task Force; Rural Health Caucus; Senate New Democrat Coalition and chair of the Rural Outreach for the Senate Democratic Caucus.

On September 9, 2009, she became Chairman of the Senate Agriculture, Nutrition, and Forestry Committee. In the Committee’s 184-year history, she was the first Arkansan and the first woman to serve as Chairman.